An 11,000-Year-Old Dog Tumor
A sexually transmitted cancer has been spreading from dog to dog for as long as 11,000 years, according to a new analysis. And today, each case of the cancer—known as canine transmissible venereal tumor (CTVT)—still retains genetic signatures of its very first host. That’s giving researchers a glimpse of the biology of the earliest domesticated dogs and insight into how a cancer can evolve over such long time periods.
“This is definitely exciting,” says cancer geneticist Elaine Ostrander of the U.S. National Institutes of Health in Bethesda, Maryland, who was not involved in the research. “Dogs have propagated and babysat and taken care of this cell line for thousands of years, and now we have an opportunity to study it.”
In 2006, researchers discovered that, unlike most cancers, CTVT doesn’t arise from mutations in an individual animal; rather, it spreads from dog to dog, primarily among feral dog populations in tropical climates. During sex between dogs, cancer cells sloughed by one animal jump to its mate, where they begin forming a new tumor, most often on the genitals. In most cases, chemotherapy is effective, but that’s not true of the only other known transmissible cancer: devil facial tumor disease (DFTD), which is ravaging Tasmanian devils in Australia. DFTD—spread when the ferocious animals bite each other—kills Tasmanian devils within months and has caused the population to decline by 70%. Research into CTVT, scientists hope, will lead to ways to stop or slow the spread of DFTD.
The 2006 CTVT study showed, based on the genetic differences between a handful of tumors, that the cancer had been jumping between animals for at least 200 years—but possibly much longer. Now that more advanced genetic technology is available, geneticist Elizabeth Murchison of the University of Cambridge in the United Kingdom wanted a more specific timeline for the emergence of the cancer. So she and her colleagues sequenced the genomes of two CTVTs, collected from dogs in Australia and Brazil. They found that—compared with the normal dog genome—the cancer contains more than 2 million mutations, far more than any known human cancer. “I was surprised by the sheer number of mutations that we found,” Murchison says. “One in two genes carries a mutation that changes the protein it encodes.”
Using previous knowledge about the average mutation rate per year for certain genes, the scientists were able to deduce that the cancer has been in existence for an estimated 11,368 years, they report online today in Science. They were also able to pinpoint genes that originated in the first host of the cancer, when it likely arose through mutations. The genes of this original dog, they concluded, suggest that it had short, dark fur and a body that resembled today’s Alaskan malamutes. Genetics couldn’t determine whether the dog was a male or female, or where it lived, but its genome did show signs of inbreeding, a potential clue as to how the tumor got started.
“If this dog was inbred, maybe it was in a very inbred overall population,” Murchison says. “If so, that may have been an environment which was especially conducive for the emergence of a transmissible cancer.”
Most cancers can’t spread between individuals because the potential recipient’s immune system detects that the cancer cells are foreign and kills them. In inbred populations, that may not be the case because individuals are more similar genetically, allowing a cancer to become transmissible. Once the tumor had evolved within multiple, similar hosts, it may have developed genetic mutations that allowed it to thrive in an even broader population, Murchison says. The tumor likely didn’t spread from an isolated population to the rest of the world until about 500 years ago, her team found.
The new research “sets the stage for future work on what properties of the tumors and of the hosts let these cancers propagate,” Ostrander says. Although there are no instances of transmissible tumors in humans today, understanding how they emerge could help ensure it remains that way, she says.
*Correction, 23 January, 3:37 p.m.: The caption and credit were incorrect; they have now been fixed.